Published online before print February 24, 2003, doi: 10.1161/01.HYP.0000057010.27011.2C
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(Hypertension. 2003;41:398.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
ACE and 
-Adducin Polymorphism as Markers of Individual Response to Diuretic Therapy
From the Department of Nephrology and Graduate School of Nephrology Universita’ Vita e Salute, Milan; and Division of Nephrology, Dialysis, and Hypertension, S. Raffaele Hospital, Milan, Italy.
Correspondence to Maria Teresa Sciarrone, Chair of Nephrology, University Vita Salute, S. Raffaele Hospital, via Olgettina 60, 20132 Milan, Italy. E-mail sciarronealibrandi.mariateresa{at}hsr.it
Renin-angiotensin system reactivity and the constitutive capacity of the renal tubule to reabsorb sodium play a role in the individual response to diuretic therapy; therefore we evaluated the blood pressure (BP) response to hydrochlorothiazide in 87 never-treated individuals with mild essential hypertension, according to ACE gene I/D and 
-adducin Gly460Trp polymorphism. These genotypes where chosen because previous data showed their interaction in determining the BP response to salt probably was the result of their involvement in the activation of the renin-angiotensin system (ACE) and in the constitutive capacity of the kidney to reabsorb sodium (-adducin) (treatment for 2 months). BP was measured after 3 run-in visits and after the first and second months of treatment by means of a standardized procedure. Data were analyzed by ANOVA, t test, and multivariate ANOVA for repeated measures (covarying for gender, age, and body mass index). Although basal mean BP (MBP) was similar in the different ACE and -adducin genotypes, patients carrying at least one I allele of ACE and one 460Trp allele of -adducin had the largest MBP decrease with treatment (12.7±1.9 mm Hg), the effect of the combination of genotypes being additive but not epistatic. These patients had an odds ratio of 15.75 of being a responder to hydrochlorothiazide compared with patients with Gly460Gly+DD, with the least MBP decrease (3.4±1.7 mm Hg). -Adducin and ACE I/D polymorphism may be useful to predict the interindividual degree of response to hydrochlorothiazide; the analysis of the combination of the 2 genotypes increases the accuracy of the prediction of response to the drug.
Key Words: genetics • renin-angiotensin system • sodium • polymorphism • hypertension, essential
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